5-Fluorouracil (5-FU) is well-established as a chemotherapeutic agent in the treatment of a variety of cancers (e.g. colon, pancreatic, breast). 5-FU irreversibly inhibits thymidylate synthase to block the synthesis of thymidine, an essential nucleotide required for DNA replication. 5-FU has been listed by the World Health Organization as one of the most important medications needed in a basic health system. However, there are many severe side effects associated with 5-FU treatment, including diarrhea, nausea, neutropenia, mouth sores, etc. Additionally, the resistance to 5-FU developed among patients also limits its clinical applications. Currently there is a need for new agents with a larger therapeutic window, lower toxicity, fewer side effects, increased solubility and/or improved pharmacokinetic profile that are useful for treating or preventing cancer.
Efficacy of active pharmaceutical ingredients (APIs) is known to be influenced by formulation methods. Among the formulation strategies being studied for solid form delivery of APIs, co-crystallization has been shown a promising means of improving physicochemical properties relative to effective drug delivery. Furthermore, a recent report on the use of a photodimer of 5-FU to function as a prodrug demonstrates the potential of delivering anticancer agents with excellent therapeutic efficacy to cancer cells, while avoiding side effects in normal cells (Q. Jin, F. Mitschang and S. Agarwal, Biomacromolecules, 2011, 12, 3684).